Our work on a-synuclein is currently focussed on applying large scale screening approaches to understand the pathobiology associated with this protein, which is now known to not only be a marker of disease but also plays an active role in disease progression. In ongoing work, we have been probing the mechanism by which a-synuclein is taken up from one cell to another, a process that has been proposed to be important in the spread of disease between brain regions. Using fluorescently labelled recombinant forms of a-synuclein we have initiated screens against uptake of the protein. Candidate modifiers are currently being validated to see if any are informative for mechanism of uptake.